ArticleThe Journal of general physiology2004
Determinants of anion permeation in the second transmembrane domain of the mouse bestrophin-2 chloride channel.
Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 72 citations in OpenAlex.
- Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing.Current medical science · 2024Article
- Structure and Function of the Bestrophin family of calcium-activated chloride channels.Channels (Austin, Tex.) · 2021Review
- Structural and functional characterization of the bestrophin-2 anion channel.Nature structural & molecular biology · 2020Article
- The TMEM16A channel mediates the fast polyspermy block inThe Journal of general physiology · 2018Article
- Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Article
- Structure and selectivity in bestrophin ion channels.Science (New York, N.Y.) · 2014Article
- Stoichiometry and specific assembly of Best ion channels.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Disease-causing mutations associated with four bestrophinopathies exhibit disparate effects on the localization, but not the oligomerization, of Bestrophin-1.Experimental eye research · 2014Article
- The bestrophin- and TMEM16A-associated Ca(2+)- activated Cl(–) channels in vascular smooth muscles.Channels (Austin, Tex.) · 2014Review
- Differential effects of Best disease causing missense mutations on bestrophin-1 trafficking.Human molecular genetics · 2013Article
- Article
- Bestrophins and retinopathies.Pflugers Archiv : European journal of physiology · 2010Review
- Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells.The Journal of biological chemistry · 2010Article
- Bestrophin-1 encodes for the Ca2+-activated anion channel in hippocampal astrocytes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Calcium-activated chloride currents in olfactory sensory neurons from mice lacking bestrophin-2.The Journal of physiology · 2009Article
- Functional properties of murine bestrophin 1 channel.Biochemical and biophysical research communications · 2009Article
- Human disease-causing mutations disrupt an N-C-terminal interaction and channel function of bestrophin 1.The Journal of biological chemistry · 2009Article
- Functional assembly and purinergic activation of bestrophins.Pflugers Archiv : European journal of physiology · 2009Article
- Bestrophin expression and function in the human pancreatic duct cell line, CFPAC-1.The Journal of physiology · 2009Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Bestrophins have been proposed to constitute a new family of Cl channels that are activated by cytosolic Ca. We showed previously that mutation of serine-79 to cysteine in mouse bestrophin-2 (mBest2) altered the relative permeability and conductance to SCN. In this paper, we have overexpressed various mutant constructs of mBest2 in HEK-293 cells to explore the contributions to anion selectivity of serine-79 and other amino acids (V78, F80, G83, F84, V86, and T87) located in the putative second transmembrane domain (TMD2). Residues selected for mutagenesis were distributed throughout TMD2, but mutations at all positions changed the selectivity. The effects on selectivity were rather modest. Replacement of residues 78, 79, 80, 83, 84, 86, or 87 with cysteine had similar effects: the permeability of the channel to SCN relative to Cl (PSCN/PCl) was decreased three- to fourfold and the relative SCN conductance (GSCN/GCl) was increased five- to tenfold. Side chains at positions 78 and 80 appeared to be situated close to the permeant anion, because the electrostatic charge at these positions affected permeation in specific ways. The effects of charged sulfhydryl-reactive MTS reagents were the opposite in the V78C and F80C mutants and the effects were partially mimicked by substitution of F80 with charged amino acids. In S79T, switching from Cl to SCN caused slow changes in GSCN/GCl (tau = 16.6 s), suggesting that SCN binding to the channel altered channel gating as well as conductance. The data in this paper and other data support a model in which TMD2 plays an important role in forming the bestrophin pore. We suggest that the major determinant in anion permeation involves partitioning of the permeant anion into an aqueous pore whose structural features are rather flexible. Furthermore, anion permeation and gating may be linked.
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